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Cancer risk associated with nuclear atypia in cytologically indeterminate thyroid nodules. A systematic review and meta-analysis.

Cancer risk associated with nuclear atypia in cytologically indeterminate thyroid nodules. A systematic review and meta-analysis.
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Valderrabano P, Khazai L, Thompson ZJ, Sharpe SC, Tarasova VD, Otto KJ, Hallanger-Johnson JE, Wadsworth JT, Wenig BM, Chung CH, Centeno BA, McIver B,


Valderrabano P, Khazai L, Thompson ZJ, Sharpe SC, Tarasova VD, Otto KJ, Hallanger-Johnson JE, Wadsworth JT, Wenig BM, Chung CH, Centeno BA, McIver B, (click to view)

Valderrabano P, Khazai L, Thompson ZJ, Sharpe SC, Tarasova VD, Otto KJ, Hallanger-Johnson JE, Wadsworth JT, Wenig BM, Chung CH, Centeno BA, McIver B,

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Thyroid : official journal of the American Thyroid Association 2017 11 21() doi 10.1089/thy.2017.0419

Abstract
BACKGROUND
Indeterminate categories of thyroid cytopathology (categories B-III and B-IV of the Bethesda system) are integrated by a heterogeneous spectrum of cytological scenarios that are generally clustered for analysis and management recommendations. It has been suggested that aspirates exhibiting nuclear atypia have a higher risk of malignancy. We assess whether cytologically indeterminate thyroid nodules with nuclear atypia have a significantly higher cancer risk than those without nuclear atypia.

METHODS
On 6/30/2016 we searched PubMed and EMBASE for articles in English or Spanish using a search strategy developed by an endocrinologist and a librarian. Case reports were excluded; and no date limits were used. References of all included studies were also screened for relevant missing studies. We included studies in which the prevalence of malignancy of cytologically indeterminate thyroid nodules with histological confirmation with and without nuclear atypia was reported. We excluded studies that included (1) nodules suspicious for malignancy, (2) nodules with non-indeterminate (B-III or B-IV) cytology on repeated biopsy, if performed; (3) nodules not consecutively evaluated; (4) cohort overlapping with another larger series. Two investigators independently assessed the eligibility and risk of bias of the studies. PRISMA and MOOSE guidelines were followed. Summary data was extracted from published reports by one investigator and independently reviewed by another. Data were pooled using a random-effects model. Heterogeneity was explored using subgroup analysis and mixed-effect model meta-regression. The odds ratio for malignancy of cytologically indeterminate thyroid nodules with nuclear atypia over cytologically indeterminate thyroid nodules without nuclear atypia was calculated.

RESULTS
Of 2,571 retrieved studies, 20 were eligible. The meta-analysis was conducted on summary data of 3,532 cytologically indeterminate thyroid nodules -1,162 with and 2,370 without nuclear atypia-. The odds ratio for malignancy in cytologically indeterminate thyroid nodules with nuclear atypia was 3.63 (3.06-4.35). There was no evidence of publication bias; and heterogeneity was insignificant (I2 <0.01%, p=0.40). CONCLUSIONS
Nuclear atypia is a significant indicator of malignancy in cytologically indeterminate thyroid nodules and needs to be standardized and implemented into clinical practice.

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